RESUMEN
AIM: Capric acid (also known as decanoic acid or C10) is one of the fatty acids in the medium-chain triglycerides (MCTs) commonly found in dietary fats. Although dietary treatment with MCTs is recently of great interest for the potential therapeutic effects on neuropsychiatric disorders, the effects of oral administration of C10 on behavior remain to be examined. This study investigated acute and chronic effects of oral administration of C10 on locomotor activity and anxiety-like and depression-related behaviors in adult male C57BL/6J mice. METHODS: To explore the acute effects of C10 administration, mice were subjected to a series of behavioral tests in the following order: light/dark transition, open field, elevated plus maze, Porsolt forced swim, and tail suspension tests, 30 minutes after oral gavage of either vehicle or C10 solution (30 mmol/kg dose in Experiment 1; 0.1, 0.3, 1.0, 3.0 mmol/kg doses in Experiment 2). Next, to examine chronic effects of C10, mice repeatedly administered with either vehicle or C10 solution (0.3, 3.0 mmol/kg doses per day, for 21 days, in Experiment 3) were subjected to behavioral tests without oral administration immediately before each test. RESULTS: The mice administrated with the high dose of C10 (30 mmol/kg) showed lower body weights, shorter distance traveled, and more anxiety-like behavior than vehicle-treated mice, and the results reached study-wide statistical significance. The C10 administration at a lower dose of 0.3 mmol/kg had no significant effects on body weights and induced nominally significantly longer distance traveled than vehicle administration. Repeated administration of C10 at a dose of 3.0 mmol/kg for more than 21 days caused lower body weights and decreased depression-related behavior, although the behavioral differences did not reach study-wide significance. CONCLUSIONS: Although these results suggest dose-dependent effects of oral administration of capric acid on locomotor activity and anxiety-like and depression-related behaviors, further study will be needed to replicate the findings and explore the underlying brain mechanisms.
Asunto(s)
Conducta Animal , Depresión , Administración Oral , Animales , Ansiedad/tratamiento farmacológico , Ácidos Decanoicos/farmacología , Depresión/tratamiento farmacológico , Ácidos Grasos/farmacología , Locomoción , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Previous clinical studies have shown that anisodamine could improve no-reflow phenomenon and prevent reperfusion arrhythmias, but whether this protective effect is related to the antagonism of the M-type cholinergic receptor or other potential mechanisms is uncertain. The aim of the present study was to investigate the role of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) in cardioprotective effect of anisodamine against ischemia/reperfusion injury. Anisodamine and 5- hydroxydecanoic acid were used to explore the relationship between anisodamine and mitoK ATP . Using a Langendorff isolated heart ischemia/reperfusion injury model, hemodynamic parameters and reperfusion ventricular arrhythmia were evaluated; in addition, changes in myocardial infarct size, cTnI from coronary effluent and myocardial ultrastructure, as well as ATP, MDA and SOD in myocardial tissues, were detected. In the hypoxia/reoxygenation injury model of neonatal rat cardiomyocyte, cTnI release in the culture medium and levels of ATP, MDA and SOD in cardiomyocytes and mitochondrial membrane potential, were analyzed. Overall, anisodamine could significantly improve the hemodynamic indexes of isolated rat heart injured by ischemia/reperfusion, reduce the occurrence of ventricular reperfusion arrhythmia and myocardial infarction area, and improve the ultrastructural damage of myocardium and mitochondria. The in vitro results demonstrated that anisodamine could improve mitochondrial energy metabolism, reduce oxidative stress and stabilize mitochondrial membrane potential. The cardioprotective effects were significantly inhibited by 5-hydroxydecanoic acid. In conclusion, this study suggests that the opening of mitoK ATP could play an important role in the protective effect of anisodamine against myocardial ischemia/reperfusion injury.
Asunto(s)
Cardiotónicos/uso terapéutico , Mitocondrias Cardíacas/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Canales de Potasio/efectos de los fármacos , Daño por Reperfusión/prevención & control , Alcaloides Solanáceos/uso terapéutico , Adenosina Trifosfato/metabolismo , Animales , Arritmias Cardíacas/prevención & control , Ácidos Decanoicos/farmacología , Metabolismo Energético/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hidroxiácidos/farmacología , Técnicas In Vitro , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Alcaloides Solanáceos/antagonistas & inhibidores , Superóxido Dismutasa/metabolismoRESUMEN
Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.
Asunto(s)
Resorción Ósea/inducido químicamente , Hueso Esponjoso/fisiopatología , Caprilatos/efectos adversos , Ácidos Decanoicos/farmacología , Dieta Cetogénica/efectos adversos , Suplementos Dietéticos/efectos adversos , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Dieta Rica en Proteínas y Pobre en Hidratos de Carbono/efectos adversos , Fémur/fisiopatología , Cuerpos Cetónicos/orina , Masculino , Ratones , Fármacos Neuroprotectores/efectos adversos , Osteoclastos/efectos de los fármacos , Distribución Aleatoria , Tibia/fisiopatología , Triglicéridos/administración & dosificaciónRESUMEN
Inflammatory response during myocardial ischemia reperfusion injury (MIRI) is essential for cardiac healing, while excessive inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanism of these uncontrolled inflammatory processes has a significant impact during the MIRI therapy. Here, we found a critical role of ATP-sensitive potassium channels (KATP) in the inflammatory response of MIRI and its potential mechanism and explored the effects of Panax Notoginseng Saponins (PNS) during this possess. Rats underwent 40 min ischemia by occlusion of the left anterior descending (LAD) coronary artery and 60 min of reperfusion. PNS was treated at the corresponding time point before operation; 5-hydroxydecanoate (5-HD) and glybenclamide (Gly) (or Nicorandil (Nic)) were used as pharmacological blocker (or nonselective opener) of KATP. Cardiac function and pathomorphology were evaluated and a set of molecular signaling experiments was tested. KATP current density was measured by patch-clamp. Results revealed that in MIRI, PNS pretreatment restored cardiac function, reduced infarct size, and ameliorated inflammation through KATP. However, inhibiting KATP by 5-HD and Gly significantly reversed the effects, including NLRP3 inflammasome and inflammatory mediators IL-6, MPO, TNF-α, and MCP-1. Moreover, PNS inhibited the phosphorylation and nuclear translocation of NF-κB in I/R myocardium when the KATP was activated. Importantly, PNS promoted the expression of subunits and activation of KATP. The study uncovered KATP served as a new potential mechanism during PNS modulating MIRI-induced inflammation and promoting injured heart recovery. The manipulation of KATP could be a potential therapeutic approach for MIRI and other inflammatory diseases.
Asunto(s)
Cardiotónicos/farmacología , Medicamentos Herbarios Chinos/química , Canales KATP/genética , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Saponinas/farmacología , Animales , Cardiotónicos/aislamiento & purificación , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ácidos Decanoicos/farmacología , Regulación de la Expresión Génica , Gliburida/farmacología , Hidroxiácidos/farmacología , Inflamación , Interleucina-6/genética , Interleucina-6/metabolismo , Canales KATP/agonistas , Canales KATP/antagonistas & inhibidores , Canales KATP/metabolismo , Masculino , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Nicorandil/farmacología , Técnicas de Placa-Clamp , Peroxidasa/genética , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Saponinas/aislamiento & purificación , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Due to the increasing resistance of various Candida species to azole drugs, particularly fluconazole, it would be of significant importance to look for alternative therapies. The aim of this study was to investigate the antifungal activity of capric acid and its in vitro interactions with nystatin and fluconazole against Candida isolates. A total of 40 Candida isolates (C. albicans, 36; C. kefyr, 2; C. tropicalis, 1; C. glabrata, 1) collected from the oral cavity of neonates with oropharyngeal candidiasis and a reference strain of C. albicans (ATCC 10231) were used in this study. Antifungal activity of capric acid and two comparator antifungal drugs, namely fluconazole and nystatin, was tested according to CLSI M27-A3/M60 method. The in vitro interaction between capric acid with fluconazole and nystatin was determined following a checkerboard method and results were interpreted using fractional inhibitory concentration index. Nystatin had the lowest minimum inhibitory concentrations (range, 0.125-8 µg/mL; geometric mean [GM], 0.6229 µg/mL) followed by fluconazole (range, 0.5-16 µg/mL; GM, 1.9011 µg/mL) and capric acid (range, 128-2,048 µg/mL; GM, 835.9756 µg/mL). When tested in combination, capric acid with fluconazole demonstrated synergistic, indifferent, and antagonistic interactions in 3 (7.317%), 24 (58.536%), and 14 (34.146%) cases, respectively. For combination of capric acid with nystatin, synergistic, indifferent, and antagonistic interactions were observed in 1 (2.439%), 19 (46.341%), and 21 (51.219%) cases, respectively. All cases of synergistic interactions were against resistant or susceptible dose-dependent isolates. Fluconazole, nystatin, and capric acid seem to be more effective when they are used alone compared with their combination. However, their combination might be effective on resistant isolates.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis Bucal/tratamiento farmacológico , Ácidos Decanoicos/farmacología , Fluconazol/farmacología , Nistatina/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Candida/aislamiento & purificación , Candidiasis Bucal/microbiología , Ácidos Decanoicos/química , Ácidos Decanoicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Fluconazol/química , Fluconazol/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Nistatina/química , Nistatina/aislamiento & purificaciónRESUMEN
BACKGROUND: Cytoprotection afforded by mitochondrial ATP-sensitive K+-channel (mKATP-channel) opener diazoxide (DZ) largely depends on the activation of potassium cycle with eventual modulation of mitochondrial functions and ROS production. However, generally these effects were studied in the presence of MgâATP known to block K+ transport. Thus, the purpose of our work was the estimation of DZ effects on K+ transport, K+ cycle and ROS production in rat liver mitochondria in the absence of MgâATP. RESULTS: Without Mg·ATP, full activation of native mKATP-channel, accompanied by the increase in ATP-insensitive K+ uptake, activation of K+-cycle and respiratory uncoupling, was reached at ≤0.5 µM of DZ,. Higher diazoxide concentrations augmented ATP-insensitive K+ uptake, but not mKATP-channel activity. mKATP-channel was blocked by Mg·ATP, reactivated by DZ, and repeatedly blocked by mKATP-channel blockers glibenclamide and 5-hydroxydecanoate, whereas ATP-insensitive potassium transport was blocked by Mg2+ and was not restored by DZ. High sensitivity of potassium transport to DZ in native mitochondria resulted in suppression of mitochondrial ROS production caused by the activation of K+-cycle on sub-micromolar scale. Based on the oxygen consumption study, the share of mKATP-channel in respiratory uncoupling by DZ was found. CONCLUSIONS: The study of mKATP-channel activation by diazoxide in the absence of MgATP discloses novel, not described earlier, aspects of mKATP-channel interaction with this drug. High sensitivity of mKATP-channel to DZ results in the modulation of mitochondrial functions and ROS production by DZ on sub-micromolar concentration scale. Our experiments led us to the hypothesis that under the conditions marked by ATP deficiency affinity of mKATP-channel to DZ can increase, which might contribute to the high effectiveness of this drug in cardio- and neuroprotection.
Asunto(s)
Adenosina Trifosfato/metabolismo , Diazóxido/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Canales de Potasio/metabolismo , Potasio/metabolismo , Animales , Ácidos Decanoicos/farmacología , Metabolismo Energético/efectos de los fármacos , Femenino , Gliburida/farmacología , Hidroxiácidos/farmacología , Transporte Iónico/efectos de los fármacos , Transporte Iónico/genética , Canales KATP/metabolismo , Magnesio/metabolismo , Mitocondrias Hepáticas/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Bloqueadores de los Canales de Potasio/metabolismo , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/genética , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study aimed to develop a pasteurization method against Salmonella enterica serovar Typhimurium in orange juice using low concentrations of naturally derived antimicrobials, ß-resorcylic acid and capric acid, under mild temperature conditions based on their synergistic bactericidal interactions. Response surface methodology was used to construct a model based on four variables, namely ß-resorcylic acid (1, 3, 5, 7, and 9 mM), capric acid (0.05, 0.10, 0.15, 0.20, and 0.25 mM), treatment temperature (35, 40, 45, 50, and 55 °C), and time (1, 2, 3, 4, and 5 min), and the resulting model was used to predict the reduction in the content of fastidious bacteria (S. Typhimurium) in orange juice and to identify the optimal treatment combination for juice pasteurization. A second-order quadratic model for Salmonella reduction showed a high regression coefficient (R2 = 0.9503), and the accuracy of the predictive model was also verified (R2 = 0.9317). The optimal conditions determined by ridge analysis were 8.43 mM ß-resorcylic acid combined with 0.10 mM capric acid at 43.46 °C for 3.03 min, and these yielded an estimated 7.41-log reduction. Treatment times <30 s under the optimal conditions also resulted in a >5.7-log reduction. The combined treatment did not affect either the pH or sugar concentration in brix, and average pH and sugar concentration values of 3.86 and 11.05% were observed, respectively. The distinct advantage of the developed method is its ability to effectively reduce the content of S. Typhimurium over a short time under low temperature conditions through the addition of consumer-preferred naturally derived antimicrobials. The predictive model could be used to determine the most cost-efficient amounts of antimicrobial agents and conditions (treatment temperature and time) for sterilizing orange juice.
Asunto(s)
Antiinfecciosos/farmacología , Citrus sinensis , Jugos de Frutas y Vegetales/microbiología , Pasteurización/métodos , Salmonella typhimurium/aislamiento & purificación , Recuento de Colonia Microbiana , Ácidos Decanoicos/farmacología , Hidroxibenzoatos/farmacología , Salmonella typhimurium/efectos de los fármacos , Temperatura , Factores de TiempoRESUMEN
Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1-3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1-3) were established using modified Mosher's method together with analysis of NMR data for their acetonide derivatives. All the isolates (1-3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.
Asunto(s)
Ascomicetos/metabolismo , Ácidos Decanoicos/química , Ácidos Decanoicos/metabolismo , Hidroxiácidos/química , Hidroxiácidos/metabolismo , Aconitum/genética , Aconitum/metabolismo , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Ascomicetos/genética , Bacterias/efectos de los fármacos , Ácidos Decanoicos/síntesis química , Ácidos Decanoicos/farmacología , Humanos , Hidroxiácidos/síntesis química , Hidroxiácidos/farmacología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Deep eutectic solvents have been recently reported as an interesting alternative to improve the therapeutic efficacy of conventional drugs, hence called therapeutic deep eutectic solvents (THEDES). The main objective of this work was to evaluate the potential of limonene (LIM) based THEDES as new possible systems for cancer treatment. LIM is known to have antitumor activity, however it is highly toxic and cell viability is often compromised, thus this compound is not selective towards cancer cells. Different THEDES based on LIM were developed to unravel the anticancer potential of such systems. THEDES were prepared by gently mixing saturated fatty acids menthol or ibuprofen (IBU) with LIM. Successful THEDES were obtained for Menthol:LIM (1:1), CA:LIM (1:1), IBU:LIM (1:4) and IBU:LIM(1:8). The results indicate that all the THEDES present antiproliferative properties, but IBU:LIM (1:4) was the only formulation able to inhibit HT29 proliferation without comprising cell viability. Therefore, IBU:LIM (1:4) was the formulation selected for further assessment of anticancer properties. The results suggest that the mechanism of action of LIM:IBU (1:4) is different from isolated IBU and LIM, which suggest the synergetic effect of DES. In this work, we unravel a methodology to tune the selectivity of LIM towards HT29 cell line without compromising cell viability of healthy cells. We demonstrate furthermore that coupling LIM with IBU leads also to an enhancement of the anti-inflammatory activity of IBU, which may be important in anti-cancer therapies.
Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Líquidos Iónicos/farmacología , Limoneno/farmacología , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Ácidos Decanoicos/química , Ácidos Decanoicos/farmacología , Ácidos Decanoicos/uso terapéutico , Composición de Medicamentos/métodos , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Ibuprofeno/química , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Líquidos Iónicos/química , Líquidos Iónicos/uso terapéutico , Limoneno/química , Limoneno/uso terapéutico , Mentol/química , Mentol/farmacología , Mentol/uso terapéutico , Ácido Mirístico/química , Ácido Mirístico/farmacología , Ácido Mirístico/uso terapéutico , Neoplasias/patologíaRESUMEN
Several studies have reported that CORM-3, a water-soluble carbon monoxide releasing molecule, elicits cardioprotection against myocardial infarction but the mechanism remains to be investigated. Numerous reports indicate that inhibition of pH regulators, the Na+/H+ exchanger (NHE) and Na+/HCO3- symporter (NBC), protect cardiomyocytes from hypoxia/reoxygenation injury by delaying the intracellular pH (pHi) recovery at reperfusion. Our goal was to explore whether CORM-3-mediated cytoprotection involves the modulation of pH regulation. When added at reoxygenation, CORM-3 (50⯵M) reduced the mortality of cardiomyocytes exposed to 3â¯h of hypoxia and 2â¯h of reoxygenation in HCO3--buffered solution. This effect was lost when using inactive iCORM-3, which is depleted of CO and used as control, thus implicating CO as the mediator of this cardioprotection. Interestingly, the cardioprotective effect of CORM-3 was abolished by switching to a bicarbonate-free medium. This effect of CORM-3 was also inhibited by 5-hydroxydecanoate, a mitochondrial ATP-dependent K+ (mKATP) channel inhibitor (500⯵M) or PD098059, a MEK1/2 inhibitor (10⯵M). In additional experiments and in the absence of hypoxia-reoxygenation, intracellular pH was monitored in cardiomyocytes exposed to cariporide to block NHE activity. CORM-3 inhibited alkalinisation and this effect was blocked by PD098059 and 5-HD. In conclusion, CORM-3 protects the cardiomyocyte against hypoxia-reoxygenation injury by inhibiting a bicarbonate transporter at reoxygenation, probably the Na+/HCO3- symporter. This cardioprotective effect of CORM-3 requires the activation of mKATP channels and the activation of MEK1/2.
Asunto(s)
Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Sustancias Protectoras/farmacología , Animales , Monóxido de Carbono/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo/química , Ácidos Decanoicos/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Flavonoides/farmacología , Humanos , Concentración de Iones de Hidrógeno , Hidroxiácidos/farmacología , Canales KATP/antagonistas & inhibidores , Canales KATP/metabolismo , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/metabolismo , Masculino , Ratones , Mitocondrias/química , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/citología , Miocitos Cardíacos/patología , Compuestos Organometálicos/uso terapéutico , Cultivo Primario de Células , Sustancias Protectoras/uso terapéuticoRESUMEN
Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid-a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.
Asunto(s)
Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Ácidos Decanoicos/farmacología , Emulsiones/farmacología , Ácidos Grasos/farmacología , Humanos , Nutrición Parenteral/métodos , Fosfolípidos/farmacología , Aceite de Soja/farmacologíaRESUMEN
Capric acid and caprylic acid are the dietary food components. They are found to inhibit the virulence factors like morphogenesis, adhesion, and biofilm formation in the human pathogenic yeast Candida albicans. Our study demonstrated that yeast-to-hyphal signal transduction pathways were affected by capric acid and caprylic acid. The expression profile of genes associated with serum-induced morphogenesis showed reduced expressions of Cdc35, Hwp1, Hst7, and Cph1 by the treatment with both the fatty acids. Cell elongation gene, Ece1, was surprisingly downregulated by 5208-fold by the treatment of caprylic acid. Nrg1 and Tup1, negative regulators of hyphal formation, were overexpressed in presence of capric or caprylic acid. Cell cycle studies revealed that capric and caprylic acids arrested cell cycle at G2/M and S phase. Targeting the virulence factors like yeast-to-hyphal transition is efficacious for treatment of opportunistic fungal infections. This research suggests that both capric and caprylic acid may be effective interventions for treating C. albicans yeast infections.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Caprilatos/farmacología , Ácidos Decanoicos/farmacología , Proteínas Fúngicas/metabolismo , Factores de Virulencia/metabolismo , Candida albicans/genética , Candida albicans/crecimiento & desarrollo , Candida albicans/metabolismo , Ciclo Celular/efectos de los fármacos , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Hifa/efectos de los fármacos , Hifa/genética , Hifa/crecimiento & desarrollo , Hifa/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Virulencia/genéticaRESUMEN
OBJECTIVES: This study was carried out to investigate the impact of various isolated phytochemical components present in the Wattakaka volubilis leaves for the growth and proliferation of human osteoblast like cells (MG63). KEY FINDINGS: Ethyl acetate was found to be the best solvent for potential extraction of phytocompounds. Further, the MTT assay was carried out to deduce the viability of 44 isolated phytochemicals. Ten phytochemical fractions found to increase the cell growth were subjected to statistical tool namely Plackett-Burman and Central composite design to screen the optimum phytochemical fraction and its dosage. The active phytochemical constituents were analysed and identified as hexadeconoic acid, octadeconoic acid, N,N-diisopropyl(2,2,3,3,3-pentafluoropropyl)amine using GC-MS and HPLC techniques. The impact of optimized concentration was assessed on osteoblast cells. The maximum % cell viability, % DNA and collagen content were found to be 164.44, 159.32 and 3.81, respectively. CONCLUSIONS: The results confirmed that the optimized fraction containing decanoic acid and isopropyl amine at particular concentration stimulated the proliferation of human osteoblast (MG63) cells. Hence, the optimized concentration of this compound from W. volubilis may used for treatment of bone related injuries externally.
Asunto(s)
Apocynaceae/química , Proliferación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Extractos Vegetales/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Colágeno/metabolismo , Ácidos Decanoicos/química , Ácidos Decanoicos/aislamiento & purificación , Ácidos Decanoicos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Humanos , Osteoblastos/metabolismo , Extractos Vegetales/química , Hojas de la Planta , Propilaminas/química , Propilaminas/aislamiento & purificación , Propilaminas/farmacologíaRESUMEN
The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how the mitoKATP channel protects against hypoxia-reoxygenation (H-R)-induced mitochondrial dysfunction in fish, we first determined the mitochondrial bioenergetic effects of two key modulators of the channel, diazoxide and 5-hydroxydecanoate (5-HD), using a wide range of doses. Subsequently, the effects of low and high doses of the modulators on mitochondrial bioenergetics and volume under normoxia and after H-R using buffers with and without magnesium and ATP (Mg-ATP) were tested. In the absence of Mg-ATP (mitoKATP channel open), both low and high doses of diazoxide improved mitochondrial coupling, but only the high dose of 5-HD reversed the post-H-R coupling-enhancing effect of diazoxide. In the presence of Mg-ATP (mitoKATP channel closed), diazoxide at the low dose improved coupling post-H-R, and this effect was abolished by 5-HD at the low dose. Interestingly, both low and high doses of diazoxide reversed H-R-induced swelling under mitoKATP channel open conditions, but this effect was not sensitive to 5-HD. Under mitoKATP channel closed conditions, diazoxide at the low dose protected the mitochondria from H-R-induced swelling and 5-HD at the low dose reversed this effect. In contrast, diazoxide at the high dose failed to reduce the swelling caused by H-R, and the addition of the high dose of 5-HD enhanced mitochondrial swelling. Overall, our study showed that in the presence of Mg-ATP, both opening of mitoKATP channels and bioenergetic effects of diazoxide were protective against H-R in fish mitochondria, while in the absence of Mg-ATP only the bioenergetic effect of diazoxide was protective.
Asunto(s)
Metabolismo Energético , Hipoxia/metabolismo , Mitocondrias/metabolismo , Oncorhynchus mykiss/metabolismo , Oxígeno/farmacología , Canales de Potasio/metabolismo , Sustancias Protectoras/metabolismo , Adenosina Trifosfato/farmacología , Animales , Tampones (Química) , Respiración de la Célula/efectos de los fármacos , Ácidos Decanoicos/farmacología , Diazóxido/farmacología , Metabolismo Energético/efectos de los fármacos , Homeostasis/efectos de los fármacos , Hidroxiácidos/farmacología , Mitocondrias/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacosRESUMEN
The total and positional fatty acid composition in camphor tree (Cinnamomum camphora) seed kernel oil (CKO) were analyzed, and for the first time, the effect of CKO on body fat deposition and blood lipids in rats was studied. The major fatty acids in CKO were determined to be decanoic acid (C10:0, 51.49%) and dodecanoic acid (C12:0, 40.08%), and uniformly distributed at Sn-1, 3, and Sn-2 positions in triglyceride (TG). Rats were randomly divided into control, CKO, lard, and soybean oil groups. At the end of the experiment, levels of blood lipids and the fats of abdomen in the rats were measured. The main organ were weighted and used for the histological examination. The results showed that body weight and fat deposition in CKO group were significantly lower than the lard and soybean groups. Moderate consumption of CKO was found to improve the levels of blood TG and low density lipoprotein cholesterol.
Asunto(s)
Grasa Abdominal/metabolismo , Peso Corporal/efectos de los fármacos , Cinnamomum camphora/química , Ácidos Decanoicos/farmacología , Ácidos Láuricos/farmacología , Lípidos/sangre , Aceites de Plantas/farmacología , Animales , LDL-Colesterol/sangre , Ácidos Decanoicos/uso terapéutico , Grasas de la Dieta/farmacología , Hiperlipidemias/metabolismo , Hiperlipidemias/prevención & control , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Ácidos Láuricos/uso terapéutico , Masculino , Obesidad/metabolismo , Obesidad/prevención & control , Aceites de Plantas/química , Aceites de Plantas/uso terapéutico , Ratas Sprague-Dawley , Semillas/química , Aceite de Soja/farmacología , Aceite de Soja/uso terapéutico , Árboles , Triglicéridos/sangreRESUMEN
A daily eatable candy that has possible protective activity against oral candidiasis was experimentally produced. The candy was made from reduced-maltose as main constituent and from several natural products, such as oligonol (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and capric acid, which are known to have anti-Candida activity in vitro and in vivo. The candy effectively inhibited the mycelial growth of C. albicans, even when it was diluted 1,000 times with culture media. We assessed the protective activity of the candy against murine candidiasis. When 50µl of candy dissolved and diluted 4 times with water was administered 3 times into the oral cavity of Candida infected mice, the score of lesions on the Candida-infected tongues improved on day 2. These findings suggest that this candy has potential as food that provides protective activity against oral candidiasis.
Asunto(s)
Candidiasis Bucal/tratamiento farmacológico , Candidiasis Bucal/microbiología , Dulces , Cassia/química , Catequina/análogos & derivados , Ácidos Decanoicos/farmacología , Monoterpenos/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Polifenoles/farmacología , Monoterpenos Acíclicos , Animales , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Candidiasis Bucal/prevención & control , Catequina/farmacología , Catequina/uso terapéutico , Codonopsis/química , Ácidos Decanoicos/uso terapéutico , Modelos Animales de Enfermedad , Combinación de Medicamentos , Farmacorresistencia Fúngica , Ácidos Grasos/farmacología , Ácidos Grasos/uso terapéutico , Glycyrrhiza/química , Maltosa/análogos & derivados , Ratones , Ratones Endogámicos ICR , Monoterpenos/uso terapéutico , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Polifenoles/uso terapéutico , Própolis , Organismos Libres de Patógenos Específicos , Almidón , Alcoholes del Azúcar , Resultado del TratamientoRESUMEN
The present study was adopted to evaluate the antioxidant efficacy of medium chain fatty acid (caprylic, capric and lauric) rich rice bran oils in comparison to rice bran oil in terms of altered biochemical parameters of oxidative stress following sodium arsenite treatment in rats. Animals were divided into ten groups; five normal groups and five arsenite treated groups. Results showed that activities of antioxidant enzymes in liver, brain and erythrocyte membrane increased with the administration of rice bran oil and MCFA rich rice bran oils both in normal and arsenite treated cases. Lipid peroxidation increased with the administration of sodium arsenite, but again administration of rice bran oil and MCFA rich rice bran oils decreased the lipid peroxidation. Caprylic acid rich rice bran oil showed the best ameliorative effects.
Asunto(s)
Antioxidantes , Arseniatos/toxicidad , Caprilatos/farmacología , Ácidos Decanoicos/farmacología , Ácidos Láuricos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Aceites de Plantas/farmacología , Animales , Antioxidantes/metabolismo , Encéfalo/enzimología , Catalasa/metabolismo , Depresión Química , Membrana Eritrocítica/enzimología , Glutatión Reductasa/metabolismo , Hígado/enzimología , Masculino , Aceites de Plantas/química , Ratas Wistar , Aceite de Salvado de Arroz , Superóxido Dismutasa/metabolismoRESUMEN
Levosimendan is a calcium-sensitizing agent shown to prevent myocardical contractile depression in various heart diseases. In this study, we investigated the effect of levosimendan on cardiac dysfunction and apoptosis in hypothermic preservation rat hearts. Isolated rat hearts were preserved in Celsior solution with or without levosimendan. The left ventricular developed pressure (LVDP) recovery rate of isolated rat heart significantly decreased, and the apoptosis index increased after 9 hours of hypothermic preservation. Supplement Celsior solution with levosimendan (10 and 10 mole/L) enhanced the LVDP recovery rate and reduced apoptosis. Levosimendan inhibited the hypothermic preservation-induced calpain activation and cleavage of Bid. Levosimendam induced increased myocardial inducible nitric oxide synthase but not endothelial nitric oxide synthase expression. A selective inducible nitric oxide synthase inhibitor 1400W, and a mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-hydroxydecanoate but not a sarcolemmal KATP channel blocker HMR-1098 prevented improvement effect of levosimendam on LVDP recovery rate, abolished the inhibitory effect of levosimendan on hypothermic preservation-induced activation of calpain, cleavage of Bid, and apoptosis. These data suggested that Celsior solution supplement with levosimendan improved cardiac function recovery and reduced myocyte apoptosis in hypothermic preservation rat hearts.
Asunto(s)
Hidrazonas/farmacología , Miocitos Cardíacos/efectos de los fármacos , Piridazinas/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Benzamidas/farmacología , Cardiotónicos/administración & dosificación , Cardiotónicos/farmacología , Ácidos Decanoicos/farmacología , Disacáridos/administración & dosificación , Disacáridos/farmacología , Electrólitos/administración & dosificación , Electrólitos/farmacología , Glutamatos/administración & dosificación , Glutamatos/farmacología , Glutatión/administración & dosificación , Glutatión/farmacología , Histidina/administración & dosificación , Histidina/farmacología , Hidrazonas/administración & dosificación , Hidroxiácidos/farmacología , Masculino , Manitol/administración & dosificación , Manitol/farmacología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Piridazinas/administración & dosificación , Ratas , Ratas Sprague-Dawley , SimendánRESUMEN
Clostridium difficile is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide; in addition, the proliferation of antibiotic-resistant C. difficile is becoming a significant problem. Virgin coconut oil (VCO) has been shown previously to have the antimicrobial activity. This study evaluates the lipid components of VCO for the control of C. difficile. VCO and its most active individual fatty acids were tested to evaluate their antimicrobial effect on C. difficile in vitro. The data indicate that exposure to lauric acid (C12) was the most inhibitory to growth (P<.001), as determined by a reduction in colony-forming units per milliliter. Capric acid (C10) and caprylic acid (C8) were inhibitory to growth, but to a lesser degree. VCO did not inhibit the growth of C. difficile; however, growth was inhibited when bacterial cells were exposed to 0.15-1.2% lipolyzed coconut oil. Transmission electron microscopy (TEM) showed the disruption of both the cell membrane and the cytoplasm of cells exposed to 2 mg/mL of lauric acid. Changes in bacterial cell membrane integrity were additionally confirmed for VCO and select fatty acids using Live/Dead staining. This study demonstrates the growth inhibition of C. difficile mediated by medium-chain fatty acids derived from VCO.
Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Ácidos Grasos/farmacología , Aceites de Plantas/farmacología , Caprilatos/farmacología , Aceite de Coco , Recuento de Colonia Microbiana , Ácidos Decanoicos/farmacología , Farmacorresistencia Bacteriana , Ácidos Grasos/análisis , Ácidos Láuricos/farmacología , Metronidazol/farmacología , Viabilidad Microbiana/efectos de los fármacos , Microscopía Electrónica de Transmisión , Aceites de Plantas/análisisRESUMEN
Extralife, a Pentaphylloides fruticos extract, in concentrations of 0.005-10 µg/ml dose-dependently increased H2O2 production in rat heart mitochondria in the presence of respiration substrates. Extralife decreased ATP-induced accumulation of H2O2 related to inhibition of mitochondrial ATP-dependent potassium channel. This effect was observed only at low doses of the adaptogen (0.05-3 µg/ml). High doses of the substance (5-10 µg/ml) did not abolish ATP-dependent production of H2O2 and increased the rate of H2O2 generation by the mitochondria. We concluded that Extralife in trace concentrations could activate mitochondrial ATP-dependent potassium channel and decrease H2O2 accumulation in the mitochondria.